A Molecular Replication Process Drives Supramolecular Polymerization

2021 ◽  
Author(s):  
Yuanning Feng ◽  
Douglas Philp
Keyword(s):  
Replication Process ◽  
Supramolecular Polymerization ◽  
Molecular Replication

An Overview of Antiretroviral Agents for Treating HIV Infection in Paediatric Population

2020 ◽  
Vol 27 (5) ◽  
pp. 760-794 ◽  
Author(s):  
Rita Melo ◽  
Agostinho Lemos ◽  
António J. Preto ◽  
Beatriz Bueschbell ◽  
Pedro Matos-Filipe ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Reverse Transcriptase ◽  
Targeted Delivery ◽  
Highly Active Antiretroviral Therapy ◽  
Antiretroviral Drugs ◽  
Viral Reservoir ◽  
Reverse Transcriptase Inhibitors ◽  
Replication Process ◽  
Antiretroviral Agents ◽  
Multiple Drugs

Paediatric Acquired ImmunoDeficiency Syndrome (AIDS) is a life-threatening and infectious disease in which the Human Immunodeficiency Virus (HIV) is mainly transmitted through Mother-To- Child Transmission (MTCT) during pregnancy, labour and delivery, or breastfeeding. This review provides an overview of the distinct therapeutic alternatives to abolish the systemic viral replication in paediatric HIV-1 infection. Numerous classes of antiretroviral agents have emerged as therapeutic tools for downregulation of different steps in the HIV replication process. These classes encompass Non- Nucleoside Analogue Reverse Transcriptase Inhibitors (NNRTIs), Nucleoside/Nucleotide Analogue Reverse Transcriptase Inhibitors (NRTIs/NtRTIs), INtegrase Inhibitors (INIs), Protease Inhibitors (PIs), and Entry Inhibitors (EIs). Co-administration of certain antiretroviral drugs with Pharmacokinetic Enhancers (PEs) may boost the effectiveness of the primary therapeutic agent. The combination of multiple antiretroviral drug regimens (Highly Active AntiRetroviral Therapy - HAART) is currently the standard therapeutic approach for HIV infection. So far, the use of HAART offers the best opportunity for prolonged and maximal viral suppression, and preservation of the immune system upon HIV infection. Still, the frequent administration of high doses of multiple drugs, their inefficient ability to reach the viral reservoirs in adequate doses, the development of drug resistance, and the lack of patient compliance compromise the complete HIV elimination. The development of nanotechnology-based drug delivery systems may enable targeted delivery of antiretroviral agents to inaccessible viral reservoir sites at therapeutic concentrations. In addition, the application of Computer-Aided Drug Design (CADD) approaches has provided valuable tools for the development of anti-HIV drug candidates with favourable pharmacodynamics and pharmacokinetic properties.

Computational Evidences of Phytochemical Mediated Disruption of PLpro Driven Replication of SARS-CoV-2: A Therapeutic Approach Against COVID-19

2020 ◽  
Vol 21 ◽  
Author(s):  
Acharya Balkrishna ◽  
Rashmi Mittal ◽  
Vedpriya Arya
Keyword(s):  
Molecular Docking ◽  
Md Simulation ◽  
Bond Distance ◽  
Immunological Response ◽  
Docking Study ◽  
Receptor Interaction ◽  
Molecular Docking Study ◽  
Replication Process ◽  
Stable Conformation ◽  
Distance Analysis

Background:: COVID-19 caused by SARS-CoV-2 has been declared as global pandemic by WHO. Comprehensive analysis of this unprecedented outbreak may help to fight against the disease and may play a pivotal role in decreasing the mortality rate linked with it. Papain like protease (PLpro), a multifunctional polyprotein facilitates the replication of SARS-CoV-2 and evades it from the host immunological response by antagonizing cytokines, interferons and may be considered as potential drug target to combat the current pandemic. Methods:: Natural moieties obtained from medicinal plants were analysed for their potency to target PLpro of SARS-CoV-2 by molecular docking study and were compared with synthetic analogs named as remdesivir, chloroquine and favipiravir. The stability of complexes of top hits was analysed by MD Simulation and interaction energy was calculated. Furthermore, average RMSD values were computed and deepsite ligand binding pockets were predicted using Play Molecule. Drug like abilities of these moieties were determined using ADMET and bond distance between the ligand and active site was assessed to predict the strength of interaction. Results:: Nimbocinol (-7.6 Kcal/mol) and sage (-7.3 Kcal/mol) exhibited maximum BA against PLpro SARS-CoV-2 as evident from molecular docking study which was found to be even better than remdesivir (-6.1 Kcal/mol), chloroquine (-5.3 Kcal/mol) and favipiravir (-5.7 Kcal/mol). Both nimbocinol-PLpro and sage-PLpro SARS-CoV-2 complex exhibited stable conformation during MD Simulation of 101ns at 310 K and potential, kinetic and electrostatic interaction energies were computed which was observed to be concordant with results of molecular docking study. RMSD average values were found to be 0.496 ± 0.015 Å and 0.598 ± 0.023 Å for nimbocinol and sage respectively thus revealing that both the deviation and fluctuations during MD Simulation were observed to be least. Deepsite prediction disclosed that both compounds occupied cryptic pockets in receptor and non-bond distance analysis revealed the formation of hydrogen bonds during ligand-receptor interaction. ADMET exploration further validated the drug like properties of these compounds. Conclusion:: Present study revealed that active constituents of Azadirachta indica and Salvia officinalis can be potentially used to target SARS-CoV-2 by hindering its replication process.

Design and in-silico screening of Peptide Nucleic Acid (PNA) inspired novel pronucleotide scaffolds targeting COVID-19

2020 ◽  
Vol 16 ◽  
Author(s):  
Bichismita Sahu ◽  
Santosh Kumar Behera ◽  
Rudradip Das ◽  
Tanay Dalvi ◽  
Arnab Chowdhury ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
In Silico ◽  
Peptide Nucleic Acid ◽  
Large Set ◽  
Nonstructural Proteins ◽  
In Silico Screening ◽  
Replication Process ◽  
Enveloped Virus ◽  
Treatment Regimens ◽  
Novel Coronavirus

Introduction: The outburst of the novel coronavirus COVID-19, at the end of December 2019 has turned itself into a pandemic taking a heavy toll on human lives. The causal agent being SARS-CoV-2, a member of the long-known Coronaviridae family, is a positive sense single-stranded enveloped virus and quite closely related to SARS-CoV. It has become the need of the hour to understand the pathophysiology of this disease, so that drugs, vaccines, treatment regimens and plausible therapeutic agents can be produced. Methods: In this regard, recent studies uncovered the fact that the viral genome of SARS-CoV-2 encodes nonstructural proteins like RNA dependent RNA polymerase (RdRp) which is an important tool for its transcription and replication process. A large number of nucleic acid based anti-viral drugs are being repurposed for treating COVID-19 targeting RdRp. Few of them are in the advanced stage of clinical trials including Remdesivir. While performing close investigation of the large set of nucleic acid based drugs, we were surprised to find that the synthetic nucleic acid backbone is explored very little or rare. Results: We have designed scaffolds derived from peptide nucleic acid (PNA) and subjected them for in-silico screening systematically. These designed molecules have demonstrated excellent binding towards RdRp. Compound 12 was found to possess similar binding affinity as Remdesivir with comparable pharmacokinetics. However, the in-silico toxicity prediction indicates compound 12 may be a superior molecule which can be explored further due to its excellent safety-profile with LD50 (12,000mg/kg) as opposed to Remdesivir (LD50 =1000mg/kg). Conclusion: Compound 12 falls in the safe category of class 6. Synthetic feasibility, equipotent binding and very low toxicity of this peptide nucleic acid derived compounds can serve as a leading scaffold to design, synthesize and evaluate many of similar compounds for the treatment of COVID-19.

Coronavirus: history, genome structure and pathogenesis

Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Poonam B ◽  
Prabhjot Kaur Gill
Keyword(s):  
Genome Structure ◽  
Public Health Research ◽  
Replication Process ◽  
Virus Family ◽  
Enveloped Virus ◽  
Target Organs ◽  
Transcription Process ◽  
Recent Emergence ◽  
The Family ◽  
Discontinuous Transcription

Background: The positive sense and inordinate large RNA genome are enclosed by helical nuceocapsids along with an outermost layer belongs to the family Coronaviridae. The phylogenetic tree of this family has been quartered into Class1 as alpha, Class 2 as beta, Class 3 as gamma and Class 4 as delta CoV. The mammalian respiratory and gastrointestinal tracts are the main target organs of this enveloped virus with misperceived mechanisms. The relevance of this virus family has considerably increased by the dint of recent emergence of the Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS), which are caused by viruses belonging to the beta-CoV group. Aim: Aforesaid illustrations of emergence of coronavirus diseases over the past two decades, SARS (2002 and 2003) and MERS (2012 to present) - the ongoing COVID-19 outbreak has pressurized the WHO to take innovative measures for public health, research and medical communities. The aim of the present review is to have proficiency in coronavirus replication and transcription process which is still in its infancy. Conclusion: An outcome of epidemics, it is being recognized as one of the most advancing viruses by the virtue of high genomic nucleotide substitution rates and recombination. The hallmark of coronavirus replication is discontinuous transcription resulting in the production of multiple subgenomic mRNAs having sequences complementary to both ends of the genome. Therefore, complete genome sequence of coronavirus will be used as frame of reference for knowing this classical phenomenon of RNA replication process. Finally, research on the pathogenesis of coronaviruses and the host immunopathological response will aid in designing vaccines and minimizing mortality rate.

Directional Supramolecular Polymerization in a Dynamic Microsolution: A Linearly Moving Polymer’s End Striking Monomers

2021 ◽  
Author(s):  
Shota Matoba ◽  
Chisako Kanzaki ◽  
Kae Yamashita ◽  
Takahiro Kusukawa ◽  
Gaku Fukuhara ◽  
...  
Keyword(s):  
Supramolecular Polymerization

scholarly journals Oriented arrangement of simple monomers enabled by confinement: towards living supramolecular polymerization

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yingtong Zong ◽  
Si-Min Xu ◽  
Wenying Shi ◽  
Chao Lu
Keyword(s):  
Activation Barrier ◽  
Degree Of Polymerization ◽  
Supramolecular Polymer ◽  
Energy Principle ◽  
Spontaneous Nucleation ◽  
Pyrene Derivatives ◽  
Multifunctional Molecules ◽  
Double Hydroxide ◽  
Supramolecular Polymerization ◽  
Kinetics Of

AbstractThe living supramolecular polymerization technique provides an exciting research avenue. However, in comparison with the thermodynamic spontaneous nucleation, using simple monomers to realize living supramolecular polymerization is hardly possible from an energy principle. This is because the activation barrier of kinetically trapped simple monomer (nucleation step) is insufficiently high to control the kinetics of subsequent elongation. Here, with the benefit of the confinement from the layered double hydroxide (LDH) nanomaterial, various simple monomers, (such as benzene, naphthalene and pyrene derivatives) successfully form living supramolecular polymer (LSP) with length control and narrow dispersity. The degree of polymerization can reach ~6000. Kinetics studies reveal LDH overcomes a huge energy barrier to inhibit undesired spontaneous nucleation of monomers and disassembly of metastable states. The universality of this strategy will usher exploration into other multifunctional molecules and promote the development of functional LSP.

scholarly journals Biomimetic Approach for the Elaboration of Highly Hydrophobic Surfaces: Study of the Links between Morphology and Wettability

Biomimetics ◽  
2021 ◽  
Vol 6 (2) ◽  
pp. 38
Author(s):  
Quentin Legrand ◽  
Stephane Benayoun ◽  
Stephane Valette
Keyword(s):  
Contact Angle ◽  
Ginkgo Biloba ◽  
Contact Angle Hysteresis ◽  
Contact Angles ◽  
Textured Surfaces ◽  
Replication Process ◽  
Wetting Behavior ◽  
Static Contact ◽  
Biomimetic Approach ◽  
Highly Hydrophobic

This investigation of morphology-wetting links was performed using a biomimetic approach. Three natural leaves’ surfaces were studied: two bamboo varieties and Ginkgo Biloba. Multiscale surface topographies were analyzed by SEM observations, FFT, and Gaussian filtering. A PDMS replicating protocol of natural surfaces was proposed in order to study the purely morphological contribution to wetting. High static contact angles, close to 135∘, were measured on PDMS replicated surfaces. Compared to flat PDMS, the increase in static contact angle due to purely morphological contribution was around 20∘. Such an increase in contact angle was obtained despite loss of the nanometric scale during the replication process. Moreover, a significant decrease of the hysteresis contact angle was measured on PDMS replicas. The value of the contact angle hysteresis moved from 40∘ for flat PDMS to less than 10∘ for textured replicated surfaces. The wetting behavior of multiscale textured surfaces was then studied in the frame of the Wenzel and Cassie–Baxter models. Whereas the classical laws made it possible to describe the wetting behavior of the ginkgo biloba replications, a hierarchical model was developed to depict the wetting behavior of both bamboo species.

scholarly journals Supramolecular Systems Containing B–N Frustrated Lewis Pairs of Tris(pentafluorophenyl)borane and Triphenylamine Derivatives

2021 ◽  
Vol 03 (02) ◽  
pp. 174-183
Author(s):  
P. Chidchob ◽  
S. A. H. Jansen ◽  
S. C. J. Meskers ◽  
E. Weyandt ◽  
N. P. van Leest ◽  
...  
Keyword(s):  
Materials Science ◽  
Supramolecular Polymers ◽  
Frustrated Lewis Pairs ◽  
Paramagnetic Resonance ◽  
Donor And Acceptor ◽  
Donor Acceptor ◽  
Noncovalent Polymers ◽  
Electron Paramagnetic ◽  
Supramolecular Polymerization ◽  
Lewis Pairs

The introduction of a chemical additive to supramolecular polymers holds high potential in the development of new structures and functions. In this regard, various donor- and acceptor-based molecules have been applied in the design of these noncovalent polymers. However, the incorporation of boron–nitrogen frustrated Lewis pairs in such architectures is still rare despite their many intriguing properties in catalysis and materials science. The limited choices of suitable boron derivatives represent one of the main limitations for the advancement in this direction. Here, we examine the use of the commercially available tris(pentafluorophenyl)borane with various triphenylamine derivatives to create supramolecular B–N charge transfer systems. Our results highlight the importance of a proper balance between the donor/acceptor strength and the driving force for supramolecular polymerization to achieve stable, long-range ordered B–N systems. Detailed analyses using electron paramagnetic resonance and optical spectroscopy suggest that tris(pentafluorophenyl)borane displays complex behavior with the amide-based triphenylamine supramolecular polymers and may interact in dimers or larger chiral aggregates, depending on the specific structure of the triphenylamines.

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